title: Evaluating amyloid-β oligomers in cerebrospinal fluid as a biomarker for Alzheimer's disease.
abstract: The current study evaluated amyloid-β oligomers (Aβo) in cerebrospinal fluid as a clinical biomarker for Alzheimer's disease (AD). We developed a highly sensitive Aβo ELISA using the same N-terminal monoclonal antibody (82E1) for capture and detection. CSF samples from patients with AD, mild cognitive impairment (MCI), and healthy controls were examined. The assay was specific for oligomerized Aβ with a lower limit of quantification of 200 fg/ml, and the assay signal showed a tight correlation with synthetic Aβo levels. Three clinical materials of well characterized AD patients (n = 199) and cognitively healthy controls (n = 148) from different clinical centers were included, together with a clinical material of patients with MCI (n = 165). Aβo levels were elevated in the all three AD-control comparisons although with a large overlap and a separation from controls that was far from complete. Patients with MCI who later converted to AD had increased Aβo levels on a group level but several samples had undetectable levels. These results indicate that presence of high or measurable Aβo levels in CSF is clearly associated with AD, but the overlap is too large for the test to have any diagnostic potential on its own.
authors.affiliation: Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden. mikko.holtta@neuro.gu.se
authors.forename: Mikko
authors.initials: M
authors.lastname: Hölttä
authors.forename: Oskar
authors.initials: O
authors.lastname: Hansson
authors.forename: Ulf
authors.initials: U
authors.lastname: Andreasson
authors.forename: Joakim
authors.initials: J
authors.lastname: Hertze
authors.forename: Lennart
authors.initials: L
authors.lastname: Minthon
authors.forename: Katarina
authors.initials: K
authors.lastname: Nägga
authors.forename: Niels
authors.initials: N
authors.lastname: Andreasen
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D000682:Amyloid / Q000134:cerebrospinal fluid; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D016022:Case-Control Studies; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid / Q000175:diagnosis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D057230:Limit of Detection; D008297:Male; D008875:Middle Aged
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D015415:Biomarkers